腰椎间盘退变性疾病与COL9A2基因多态性的关系

目的 探讨COL9A2基因多态性与腰椎间盘退变性疾病(DDD)的关系.方法 采用"病例-对照"研究方法:125例中国汉族DDD患者(DDD+)与126例中国汉族非DDD受访者(DDD-),用SNP分型系统-SNPstream UIT(Cenotyping System)对所有样本的所选SNP位点行基因型鉴定.对检测数据分别行拟和优度x2检验、基于等位基因频率/基因型的关联分析.结果 共筛查SNPl(rs12722877)、SNP2(rs3737820)、SNP3(rs209914)和SNP4(rs6676013)4个位点.病例组中和对照组中,两个位点的基因型分布均符合Hardy-Weinberg平衡;病例/对照组中等位基因频率分别为:SNP1C=228(91%)/22(9%)、SNP1G=235(93%)/17(7%),SNP2A=214(86%)/36(14%)、SNP2T=223(89%)/27(11%),SNP3A=237(95%)/13(5%)、SNP3C=238(94%)/14(6%),SNP4C=30(12%)/220(88%)、SNP4T=26(10%)/226(90%),差异无统计学意义(P＞0.05).病例/对照组中基因型频率差异无统计学意义(P＞0.05).结论 COL9A2基因可能不是决定中国汉族人群腰椎DDD的主要危险因素.

Abstract：

Objective To investigate the association between COL9A2 gene polymorphism with lumbar degenerative disc disease (DDD) in Chinese Han population. Methods A total of 125 DDD patients (58 males and 67 femals, aged 51.8 + 10. 6), and 126 controls matched in sex and age (64 males,62 femals, aged 45.7 + 8. 2) were recruited in the case-control study. Peripheral blood was collected for DNA isolation. Results Based on NCBI Genebank, corresponding single nucleotide polymorphisms-SNP1 ( rs12722877), SNP2 ( rs3737820), SNP3 (rs209914) and SNP4 (rs6676013) were identified. Hardy-Weinberg equilibrium was analyzed in both case and control groups. Genotying of all selected SNPs was done by SNPstream technology. The association analysis between phenotyepes and SNPs was conducted.Reslults NPI (rs12722877), SNP2 (rs3737820), SNP3 (rs209914) and SNP4 (rs6676013) were genttyped, and the polymorphisms distributed in line with Hardy-Weinberg equilibrium in case and contral groups. There was no significant difference in allele frequency of SNP1C, SNPIG, SNP2A, SNP2T,SNP3A, SNP3C, SNP4C and SNP4T between case group (91%, 93%, 86%, 89%, 95%, 94%, 12%,and 10%, respectively) and control group (9%, 7%, 14%, 11%, 5%, 6%, 88%, and 90% respectively). No significant difference in genotype frequencies of SNP was found between case group and control group, too (all P＞0.05). Conclusion COL9A2 gene may not be associated with lumbar DDD in ChineseHan population.     

Asociación entre los polimorfismos de genes de mieloperoxidasa y la susceptibilidad a cáncer de próstata: un estudio caso-control en la población de nacionalidad china

Background and objectivesProstate cancer (PCa) is the most common cancer among men in most western populations. The polymorphisms of the myeloperoxidase (MPO) gene have been correlated with abnormal MPO expression and increased risk of various types of cancers. Our study aimed to evaluate the association between the genetic polymorphisms and the risk of prostate cancer.MethodsGenotyping was carried out by using the genotyping system (MassARRAY iPLEX; Sequenom, Inc., San Diego, CA, USA) on 1,108 PCa patients and 1,525 cancer-free controls in a Chinese Han population.ResultsAlthough one SNP (rs8082134, P < 0.050) was significant, it is very rare and unstable. Other SNPs had no significant difference between genotype distributions in the PCa patients and the control group. Totally, SNPs in the MPO gene is not associated with PCa risk.ConclusionOur data showed a limited association between the MPO SNPs and the susceptibility to PCa in population of Chinese Han population. The possible association of rs8082134 of MPO with PCa risk need further clarification.     

The association between metabolic syndrome and lower urinary tract symptoms suggestive of benign prostatic hyperplasia in aging males: evidence based on propensity score matching

BackgroundTo investigate the association between lower urinary tract symptoms suggestive of benign prostate hyperplasia (LUTS/BPH) and metabolic syndrome (MetS) in aging Chinese males.MethodsA dataset that included 3,568 non-MetS cases and 1,020 MetS cases (after data cleansing) was downloaded from the China Health and Retirement Longitudinal Study (CHARLS). To balance the intergroup covariates, propensity score matching (PSM) was employed in the analyses. Univariate logistic regression and multivariate logistic regression were then performed to investigate the relationship between LUTS/BPH and MetS in aging Chinese males.ResultsBefore PSM, multivariate logistic regression showed that participants with MetS had a 1.47 times higher risk of LUTS/BPH compared to non-MetS cases in the final model (P<0.001). It also revealed that participants with low high-density lipoprotein (HDL), abdominal adiposity, or high triglycerides had a higher probability of LUTS/BPH [odds ratio (OR) =1.56 for low HDL; OR =1.50 for abdominal adiposity; and OR =1.48 for high triglyceride, P<0.001], while participants with hyperglycemia or hypertension had identical odds of LUTS/BPH (P>0.05). After PSM, 1,000 pairs were successfully matched. It was also found that MetS cases had a 1.60 times higher risk of LUTS/BPH compared to non-MetS cases (P<0.001), and participants with low HDL, abdominal adiposity, high triglycerides, or hyperglycemia had a higher likelihood of LUTS/BPH than their counterparts (P<0.001). However, the probability of LUTS/BPH in hypertensive patients remained similar to that in non-hypertensive patients (P>0.05).ConclusionsAging Chinese males with MetS had a higher probability of LUTS/BPH. Also, patients with low HDL, abdominal obesity, high triglycerides, or hyperglycemia had an increased risk of LUTS/BPH; however, this was not the case for hypertensive patients.     

雌激素受体β的单核苷酸多态性与前列腺癌风险的相关性研究

目的研究雌激素受体β(ERβ)的单核苷酸多态性(SNPs)与前列腺癌(CaP)风险的相关性。方法对40例CaP患者和86例正常对照者利用直接测序法对ERβ基因中的4个SNPs(近端启动子上游的3个SNPsrs3829768,rs1271572,rs3841304和外显子7上的SNPsrs1256049)进行基因分型,分析单个位点的等位基因和基因频率是否与CaP相关。结果由于不符合HardyWeinberg平衡,SNP位点rs3841304被排除。发现在CaP患者中,近端启动子上游的SNPs位点rs3829768(A/G)的G和rs1271572(C/A)的A等位基因频率及其基因型频率均显著低于正常对照者(P<0.01)。结论ERβ基因近端启动子上游有2个SNPs与汉族CaP之间存在显著的相关性。     

The TERT locus genotypes of rs2736100-CC/CA and rs2736098-AA predict shorter survival in renal cell carcinoma

Objectives

The single nucleotide polymorphisms (SNPs) at the TERT rs2736100 and rs2736098 are associated with multicancer susceptibility, however, published findings regarding renal cell carcinoma (RCC) risk are conflicting. In addition, the potential of these SNPs to predict outcomes in RCC remains unclear. The present study is designed to address these questions.

趋化因子受体6基因与陕西汉中地区类风湿关节炎汉族人群相关性

目的探讨趋化因子受体6基因单核苷酸多态性位点与中国陕西汉中地区类风湿关节炎汉族人群的相关性。 方法采用病例-对照研究方法,收集768例RA患者和960例正常对照DNA样本;用聚合酶链反应（PCR）法扩增目的条带,使用单碱基延伸法（SnapShot）对rs1331301、rs1556413、rs3093024、rs1854853和rs3093023位点基因分型,分析与RA的相关性。 结果CCR6基因5个标签SNP位点均符合哈迪温伯格平衡（HWE）,RA组和对照组基因型差异均无统计学意义（P > 0.05）。rs3093024位点A等位基因（OR = 1.22、P = 0.003）,显性模式（OR = 1.33、P = 0.0048）RA组与对照组差异具有统计学意义。rs1854853位点A等位基因（OR = 1.20、P = 0.0067）,显性模式（OR = 1.35、P = 0.0063）,RA组与对照组差异具有统计学意义。rs3093023位点T等位基因（OR = 1.26、P = 0.0009）,显性模式（OR = 1.38、P = 0.0015）,隐性模式（OR = 1.33、P = 0.025）,RA组与对照组差异有统计学意义。rs1331301和rs1556413两个SNP位点等位基因和显性、隐性模式,RA组与对照组差异均无统计学意义。 结论CCR6基因rs3093023、rs3093024和rs1854853三个单核苷酸多态性位点,可能是陕西汉中地区汉族人类风湿关节炎的易感基因位点。     

The involvement of ADAMTS‐5 genetic polymorphisms in predisposition and diffusion tensor imaging alterations of lumbar disc degeneration

Purpose: Low back pain is a global health problem in which more than 40% is caused by lumbar intervertebral disc degeneration (LDD). ADAMTS‐5 (A disintegrin and metalloproteinase with thrombospondin motifs‐5) was shown to be involved in LDD by functional analyses. To identify whether there is an association between ADAMTS‐5 and LDD, and what is the contribution of ADAMTS‐5 genetic polymorphisms to MD (Mean diffusivity) changes in lumbar IVD (Intervertebral disc). We firstly genotyped selected ADAMTS‐5 SNPs (Single nucleotide polymorphisms) in a Chinese Han population. After the primary analyses of allelic, genotypic, and haplotypic association, we performed SNP–SNP interaction analysis. We subsequently genotyped another 50 participants and acquired the corresponding MD values from individual lumbar IVDs. The association analysis between the genotypic groups divided by the above positive SNPs and the corresponding MD values were also performed. Significant associations were identified in rs151058, rs229052, and rs162502. None of the 2‐SNP haplotypic analysis survived the 10,000 permutation test. The following interaction analysis demonstrated that rs151058 was strong associated with LDD when conditioning on rs162502. Significant difference of MD values between AA and G+ carriers was identified in rs162502. This is the first study indicating that the SNPs of ADAMTS‐5 may contribute to predisposition of LDD. An interaction between rs151058 and rs229052 may exist in ADAMTS‐5 with LDD. The rs162502 might be associated with altered MD values. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:686–694, 2014.     

1667例汉族前列腺癌人群前列腺癌易感性基因多态性验证分析

目的:前列腺癌在工业化国家发病率居男性恶性肿瘤首位,在我国前列腺癌近年发病率不断上升,成为泌尿系统常见恶性肿瘤。本文通过前列腺癌基因多态性分析研究汉族人群前列腺癌易感性危险位点。方法:取1 667例前列腺癌患者与1 525例对照组外周血样双盲利用Sequenom技术进行40个前列腺癌危险位点的SNP分析。结果:40个公认的前列腺癌位点检测结果有16个位点与前列腺癌明显相关(P<0.05);同时发现在不同人种中位于8q24的1、2、5位点与10q11的MSMB编码区及22q13.2编码TTLL1/BIK区域共同决定前列腺癌易感性。结论:汉族前列腺癌人群前列腺癌基因多态性分析结果显示:rs1465618、rs721048、rs12621278、rs7679673、rs12653946、rs339331、rs1512268、rs10086908、rs16901979、rs1447295、rs10993994、rs10896449、rs902774、rs9600079、rs11649743、rs5759167与前列腺癌易感性明显相关。     

Association and meta‐analysis of HLA and non‐obstructive azoospermia in the Han Chinese population

The exact aetiology and pathogenesis of most non‐obstructive azoospermia (NOA) are still unknown. The previous two genomewide association studies (GWASs) have identified three different loci within the HLA region for NOA in the Han Chinese population, including rs3129878, rs498422 and rs7194. To further validate the risk of three GWAS‐linked loci for NOA, we conducted a case–control study of these three risk loci in an independent Han Chinese male population, with 603 NOA patients and 610 controls. Furthermore, we also performed a meta‐analysis of five studies on these three NOA‐risk loci. The case–control study strongly suggested a significant association between loci rs3129878, rs498422 and rs7194 and NOA (P = 6.75 × 10^?21 (OR = 2.2586), P = 0.0060 (OR = 1.4013) and P = 0.0128 (OR = 1.2626) respectively). Our meta‐analyses also supported the susceptibility of these three risk loci to NOA (P < 0.01). The risk variants within the HLA region potentially have a strong effect on males at risk of NOA, and may serve as diagnostic markers for male infertility. However, considering genetic difference between different populations, future validating studies in larger independent samples and animal experiments are suggested.     

Nitric oxide synthase 2 gene polymorphisms are associated with prostatic volume in Korean men with benign prostatic hyperplasia

The precise aetiology of benign prostatic hyperplasia （BPH） remains unclear; however, it is known that immunological inflammatory processes have a role in the pathogenesis of BPH initiation and progression. Nitric oxide synthase 2 （NOS2） inducible expression is closely correlated with prostatic disease, including prostate cancer and BPH. The aim of this study was to investigate the relationship between NOS2 polymorphisms and BPH. With a cohort of 205 controls and 229 BPH subjects, we genotyped three single nucleotide polymorphisms （SNPs） in the NOS2 gene, including rs2779248 （promoter, -278 T/C）, rs 10459953 （5＇-untranslated region） and rs2297518 （exon 16, missense, Ser608Leu）, using direct sequencing and restriction fragment length polymorphism. The genotypic and allelic frequencies between control and BPH subjects were compared, and the associations among the BPH subjects were analyzed. SNPStats, SNPAnalyzer and HelixTree programmes were used to analyze SNPs. There was no association on SNPs between control and BPH subjects. When BPH subjects were analyzed, there was no association on SNPs between the low and high prostate-specific antigen groups. However, one SNP （rs 10459953, odds ratio [OR] = 0.44, 95% confidence interval [CI] = 0.29-0.65, P 〈 0.0001, in codominant model; OR = 0.23, 95% CI = 0.12-0.46, P 〈 0.0001, in dominant model; and OR = 0.46, 95% CI = 0.24-0.86, P = 0.015, in recessive model） was associated with prostatic volume in BPH. We detected a strong association in genotype frequencies of NOS2 SNP （rs10459953） between subjects with small and large prostatic volume in BPH. The result suggests that NOS2 may be associated with prostatic volume in BPH.     

TERT基因多态性及HP感染与胃癌遗传易感性的研究

目的：探讨端粒酶逆转录酶（TERT）基因rs2075786单核苷酸多态性（SNP）、幽门螺杆菌（HP）与胃癌遗传易感性的关系。方法：采用聚合酶链反瘦一限制性片段长度多态性（PCR—RFLP）法分析297例胃癌患者、105例萎缩性胃炎患者及402例非萎缩性胃炎患者的基因多态性,采用病理学诊断和13C尿素酶呼气试验（13C—UBT）检测幽门螺杆菌（Hp）感染。结果：rs2075786位点CC、TC、TT基因型频率在对照组与萎缩性胃炎组分布差异无统计学意义,胃癌组TT基因型频率显著高于对照组（25．6％VS125％）,TT基因型携带者患胃癌风险增加2．23倍（95％CI：1．46～3．40）,对照组、萎缩性胃炎组、胃癌组HP感染率分别为40．3％、64．8％、56．9％,差异有统计学意义（P〈0．01）,OR值分别为2．73（95％CI：1．74～426）、196（95％CI：1．44～2．67）。经Logistic回归分析,发现Hp感染与基因突变无明显交互作用。结论：TERT基因rs2075786基因多态性与胃癌遗传易感性有关。     

Replicative study of GWAS TP63C/T,TERTC/T,and SLC14A1C/T with susceptibility to bladder cancer in North Indians

ObjectiveGenome-wide association studies have confirmed association of TP63C/T rs710521, TERTC/T rs2736098, and SLC14A1C/T rs17674580 gene variants with susceptibility to bladder cancer (BC) in European and White population. However, the risk conferred for BC for above gene variants in North Indians is unknown. We therefore, studied the association of TP63C/T, TERTC/T, and SLC14A1C/T single nucleotide polymorphisms (SNPs) with a risk of BC susceptibility in North Indian cohort.Material and methodsIn histologically confirmed 225 BC cases and 240 healthy controls, 3 SNPs were genotyped by real-time polymerase chain reaction. To evaluate the SNP effects on BC susceptibility, odds ratio (OR) and CI 95% were calculated.ResultsIn case of TP63C/T, the variant genotype (TT) showed significant reduced risk for BC (P = 0.045, OR = 0.53). Combining heterozygous and variant genotypes also demonstrated reduced risk for BC (P < 0.001, OR = 0.54). In case of TERTC/T, heterozygous genotype (CT) as well as variant genotype (TT) showed significant risk for BC susceptibility (P = 0.031, OR = 1.77 and P = 0.004, OR = 2.78, respectively) along with T allelic level (P<0.001, OR = 4.19). Furthermore, in case of SLC14A1C/T gene polymorphism, the variant genotype (TT) showed significant high risk for BC susceptibility (P = 0.006; OR = 3.01) along with variant T allelic level (P = 0.003, OR = 1.52). Interestingly, smoking was also found to modulate risks for BC in case of TERT and SLC14A1 variant genotype (TT). Further clinical confounding factor, namely, tumor grade/stage level of cases, supports the genotypic data with TERT and SLC14A1 showing a risk for BC susceptibility.ConclusionOur results suggested that polymorphism in TERTC/T and SLC14A1C/T confirmed high risk for BC in North Indian population. However, TP63C/T showed reduced risk of BC susceptibility. More replicate studies with large sample size and diverse ethnicity are required to validate these observations.     

Genotype polymorphisms of genes regulating nitric oxide synthesis determine long-term arteriovenous fistula patency in male hemodialysis patients

Objectives Nitric oxide (NO) is a pivotal vasoactive substance modulating arteriovenous fistula (AVF) patency for hemodialysis (HD). Since genetic background could be the predicting factor of AVF malfunction, we aimed to investigate whether the NO-related genotype polymorphisms determine AVF survival rates. Methods This is a retrospective, observational, multi-center study involving eight HD units in Taiwan, enrolled 580 patients initiating maintenance HD via AVFs. Genotype polymorphisms of NO-biosynthesis regulating enzymes (DDAH-1, DDAH-2, eNOS and PRMT1) were compared between HD patients with (n?=?161) and without (n?=?419) history of AVF malfunction. Subgroup analyses by gender were performed to evaluate the genetic effect in difference sexes. Results In overall population, statistically significant associations were not found between AVF malfunction and the genetic polymorphisms. In the male subgroup (n?=?313), a single nucleotide polymorphism (SNP) of PRMT1, rs10415880 (IVS9-193 A/G), showed a significant association with AVF malfunction. Male patients with AA/AG genotype had inferior AVF outcomes compared to GG genotype, regarding primary patency (70.6% vs. 40.9%, p?=?0.001), assisted primary patency (81.0% vs. 58.4%, p?p?p?Conclusions rs10415880, the SNP of PRMT1 could be a novel genetic marker associated with AVF malfunction risk in male HD patients. Those with AA and AG genotypes of rs10415880 may predict a poorer long-term patency of AVF.     

Association of receptor activator of nuclear factor-kappaB ligand (RANKL) gene polymorphisms with the susceptibility to ankylosing spondylitis: a case–control study

Objectives

To investigate the association between receptor activator of nuclear factor-kappaB ligand (RANKL) gene polymorphisms and the susceptibility to ankylosing spondylitis (AS) in a Chinese Han population.

Methods

Three hundred and fifty-two AS patients and 299 age- and gender-matched controls were recruited in this study. Peripheral blood samples were collected from all the subjects and the genomic DNA was then extracted. Three single nucleotide polymorphisms (SNPs) of the RANKL gene (rs2277438, rs7984870 and rs9533156) were genotyped using the TaqMan assay. The frequencies of alleles and genotypes were compared between AS patients and normal controls.

Results

The distributions of genotype frequencies in rs2277438 were significantly different between AS patients and normal controls (P < 0.05). The frequency of G allele of SNP rs2277438 in AS patients was significantly higher than that in normal controls (P < 0.05). The frequencies of genotypes with G allele (GG and AG) were significantly higher in AS patients when compared with normal controls (OR = 1.573, 95 % CI 1.151–2.150, P < 0.05). Neither the genotype frequencies nor the allele frequencies of rs7984870 and rs9533156 were found to be significantly different between AS patients and normal controls (P > 0.05).

Conclusions

The current study demonstrated that SNP rs2277438 of the RANKL gene was associated with the susceptibility of AS in a Chinese Han population. Genotypes with G allele (GG and AG) were identified as the risk factors for the occurrence of AS.     

Association between ADAMTS‐4 gene polymorphism and lumbar disc degeneration in Chinese Han population

Low back pain (LBP) is a common health problem and many LBP are caused by lumbar disc degeneration (LDD). ADAMTS‐4 (a disintegrin and metalloprotease with thrombospondin motifs‐4), also known as aggrecanse‐1, plays a core role in degeneration of extracellular matrix in LDD. To investigate the association between ADAMTS‐4 genetic polymorphism and LDD, we genotyped SNPs in and around ADAMTS‐4. We recruited 482 sporadic cases of LDD and 496 healthy controls from Chinese Han population. Five SNPs were selected and phenotyped by the Sequenom MassARRAY system. Allelic, genotypic, and haplotypic association was performed. Rs4233367 (c.1877 C>T), which located in exon of ADAMTS‐4 showed significant association with LDD. The T allele conferred a lower risk of LDD with an OR of 0.69 and TT genotype is at nearly one‐fifth of the risk compared to CC genotype. Other tested SNPs didn't show significant difference between the case and control groups. The SNP rs4233367 in the exon of ADAMTS‐4 gene may be associated with lumbar disc degeneration. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:860–864, 2016.     

中国北方汉族人群中MMPs基因多态性与非创伤性股骨头坏死遗传易感性的关联分析

目的筛查MMPs系统中可能与非创伤性骨坏死发病相关的单核苷酸多态性（SNP）位点，为骨坏死的早期诊断和预防提供遗传学依据。 方法在这项病例-对照研究中，设计非创伤性骨坏死病例组585例，对照组507例，分别提取外周血基因组DNA，应用MassARRAY分型技术对所选MMPs系统中9个基因上的42个SNP位点进行分型，并用卡方检验和SNPStats软件对SNP分型结果进行统计分析，评估所选位点与骨坏死发病的关联性。 结果在中国北方汉族人群中，MMP8基因上的rs11225394、MMP3基因上rs522616可能与增加骨坏死的发病风险相关，MMP3基因上的rs650108、MMP9基因上的rs2274755可能与降低骨坏死的发病风险相关。另外，我们在单倍体分析中还发现MMP9基因中rs3918249，rs2274755，rs3918254三个位点的"TGC"、"CTC"单体型较野生单体型携带者降低骨坏死发病风险更显著。 结论MMP3、MMP8、MMP9基因多态性与非创伤性骨坏死发病的遗传易感性相关。     

Genetic risk factors for post-transplantation diabetes mellitus in Chinese Han renal allograft recipients treated with tacrolimus

BackgroundPost-transplantation diabetes mellitus (PTDM) is a serious metabolic complication after kidney transplantation. The aim of this study was to explore the association of clinical variables and five selected single nucleotide polymorphisms (SNPs) with PTDM in Chinese Han renal allograft recipients taking tacrolimus (TAC).MethodsA total of 129 non-diabetic, primary, Chinese Han renal allograft recipients treated with TAC were enrolled. Five SNPs (CYP3A5 rs776741, rs776746, rs15524, CYP24A1 rs2296241, and PPARG rs1801282) were genotyped and analyzed.ResultsAmong 129 recipients, 17 (13.2%) developed PTDM. Both univariate and multivariate analysis demonstrated that age over 50 years old and CYP24A1 rs2296241 A allele were independently correlated with the development of PTDM, while no significant differences was observed in TAC pharmacokinetics and CYP3A5, PPARG polymorphisms between two groups.ConclusionsPatients with advanced age and CYP24A1 rs2296241 A allele had an increased risk of PTDM after kidney transplantation.     

Intronic RET gene variants in Down syndrome-associated Hirschsprung disease in an African population

BackgroundClinical association between Hirschsprung disease (HD) and Down syndrome (DS) is well established. RET promoter and intron 1 variations have been shown to interfere with RET function, increasing the risk of HD pathogenesis. The intronic single-nucleotide polymorphism 2 (SNP2 [rs2435357]) has been associated with DS-associated HD (DS-HD). This study focuses on variations of specific RET intron, 1 SNPs (viz, SNP1 [rs2506004] and SNP2 [rs2435357]) in DS-HD.Patients and MethodsDNA was extracted from paraffin-embedded tissue samples and whole blood in 14 patients with DS with histologically proven HD. Polymerase chain reaction products of RET intron 1 were screened for genetic variation and matched to DS and controls from the general population.ResultsThirty-seven blood and/or tissue from 14 patients with DS-HD were investigated. RET intronic variations (SNP1 [rs2506004] or SNP2 [rs2435357]) were detected in all patients. SNP1 was detected in all patients, was heterozygous in 9, and homozygous in 5 samples (all aganglionic and 1 total colonic aganglionosis). SNP2 was absent in 6 patients, heterozygous in 6, and homozygous in 3. Three DS controls had a heterozygous SNP1. Homozygous intronic SNP RET variations were related to aganglionic tissue but not normally ganglionated or transitional zone from the same individual.ConclusionsPotential disease-related RET mutations were identified in the intron region in 80% of patients with DS-HD investigated, suggesting a causal relationship. The presence of a homozygous form in the aganglionic tissue probably represents a somatic mutation, which suggests local microenvironmental factors in HD pathogenesis.     

Association of rs11190870 near LBX1 with adolescent idiopathic scoliosis susceptibility in a Han Chinese population

Purpose

To investigate whether rs11190870 near LBX1 correlates with the susceptibility or curve progression of adolescent idiopathic scoliosis (AIS) in a Han Chinese population.

Methods

A total of 949 AIS patients and 976 age-matched healthy controls were recruited. All the subjects were genotyped using the PCR-based invader assay. Case–control study and case-only study were performed to define the contribution of rs11190870 to predisposition and curve severity of AIS. Additionally, we further conducted a meta-analysis of the study findings together with those of previously reported studies.

Results

A significant association of rs11190870 with AIS was observed in the Han Chinese population (P = 1.8 × 10⁻⁹; odd ratio = 1.51; 95 % confidence interval = 1.33–1.71), and AIS patients with TT genotype had a larger Cobb angle than those with TC or CC genotype (P = 0.005). The meta-analysis confirmed that the positive association of this SNP with AIS in the East Asian population.

Conclusions

The SNP rs11190870 near LBX1 is associated with both susceptibility and curve progression of AIS.